Process fur preparing bl



United States Patent Office 3,210,367 Patented Oct. 5, 1965 3,210,367PROCESS F011 PREPARING BIPYRIDYLS Frank Raymond Bradbury and AlastairCampbell, Widnes,

England, assignors to Imperial Chemical Industries Limited, Millbank,London, England, a corporation of Great Britain No Drawing. Filed Mar.13, 1963, Ser. No. 264,779

Claims priority, application Great Britain, Mar. 14, 1962, 9,805/ 62 14Claims. (Cl. 260296) This invention relates to the manufacture oforganic bases, and more particularly to the manufacture of hipyridyls.

It is known that bipyridyls can be prepared by oxidation ofsodium-pyridine interaction products, and copending application, SerialNo. 194,723, filed May 14, 1962 describes particular conditions for thisreaction which improve the yield of bipyridyls, and especially of the4:4- isomer. In our copending applications, Serial No. 193,627, filedMay 9, 1962 and Serial No. 221,899, filed September 6, 1962 there arealso described processes for the manufacture of bipyridyls by oxidationof magnesium/pyridine and aluminium/pyridine interaction productsrespectively.

We have now found that the conventional oxidation step used for theconversion of metal-pyridine interaction products to bipyridyls can bedispensed with, and replaced by a treatment with water, in thesubstantial absence of an oxidising agent such as air or oxygen. Thisprocess provides bipyridyls in subtsantially undiminished yield comparedwith the earlier route, and avoids the lengthy air oxidation procedureand the use of conventional oxidising agents.

It is known to treat a sodium-pyridine interaction product with moistether (Emmert: Ber. 1917, 50, 31). The product so treated was made byinteracting sodium with excess pyridine and then removing excesspyridine (both operations at substantially room temperature) and thenheating the residual sodium-pyridine interaction product under reducedpressure to convert it into a second sodiumpyridine interaction product.In this procedure, the product obtained is not a bipyridyl but atetrahydrobipyridyl. We have found that 'bipyridyls can be obtained asthe product has been heated to an elevated temperature with freepyridine before the water treatment is carried out.

Thus according to our invention we provide a process for the manufactureof bipyridyls which comprises treating with water a metal-pyridineinteraction product which has been heated to an elevated temperature inthe presence of a free pyridine.

The elevated temperature to which the mixture of metal-pyridineinteraction product and the pyridine is heated before the watertreatment should be at least 70 C. An upper limit is usually set by theboiling point of the mixture, though this may be increased if desired byheating under pressure or adding higher-boiling diluents. In the case ofa very reactive metal such as sodium which can react with a pyridinebelow this temperature, heat should be applied if necessary to raise thetemperature of the mixture appropriately. This heating may be during orafter interaction. In the case of less reactive metals such as aluminiumand magnesium, the necessary elevated temperature is usually achievedduring the metalpyridine interaction stage. The period of heating andthe proportions of pyridine used may be those more fullydescribed incopending applications, Serial No. 194,723, Serial No. 193,627 andSerial No. 221,899 for the production of metal-pyridine interactionproducts.

The free pyridine may be in particular an excess of the pyridine used informing the metal-pyridine interaction product.

The pyridine is preferably pyridine itself, but any other pyridinereactive towards the selected metal may be used if desired, for examplealkylpyridines. In general, alkylpyridines are less reactive thanpyridine in this process.

The metal-pyridine interaction product may be in particular asodium-pyridine, a magnesium-pyridine or an aluminium-pyridineinteration product though interaction products derived from other metalsreactive towards the pyridine may be used if desired, for example thosederived from other alkali metals. These interaction products may beproduced by interacting the metal and pyridine with heating andoptionally in the presence of a diluent (which may be an excess of thepyridine and for an inert organic liquid for example trimethyl benzene,as is more fully described in copending applications, Serial No.193,627, Serial No. 194,723 and Serial No. 221,899. respectively. Themetals used for this purpose may be pure or contain alloying metals. Theinteraction of magnesium with pyridine may be slow to start and may beinitiated by addition of a small proportion of an initiator,particularly a material which can induce the formation of free radicalsin the mixture, for example sodium, potasssium, bromine or iodine;likewise the interaction of aluminium and pyridine may be initiated by acompound which can break down the surface oxide film on the metal, forexample a mercury compound, particularly mercuric chloride, optionallyin conjunction with an initiator capable of forming free radicals in themixture.

We prefer to carry out the process of our invention using ametal-pyridine interaction product from which the excess of the pyridineused in its production is not removed before the treatment with water.In this Way, problems arising from the isolation of the metal-pyridineinteraction product are avoided. In the case of sodiumpyridineinteraction products, which are violently explosive in contact with air,this avoidance of isolation is especially valuable from the safetyaspect.

The treatment of the metal-pyridine interaction product with water ispreferably carried out at an elevated temperature which is at least 40C., and especially is in the range C. to C. The upper temperature limitis usually defined by the boiling point of the reaction mixture, andthis boiling point may be raised above 120 C., for example by additionof higher boiling diluents such as dimethylaniline or by use ofsuperatmospheric pressures. Accordingly the process of our invention canbe carried out at temperatures above 120 C. if desired, but noadditional overall advantage is usually achieved by doing so. Below 40C. there is a tendency for the reaction mixture to become thick andlumpy, so that satisfactory completion of the reaction is difficult toachieve.

The treatment of the metal-pyridine interaction product with water maybe carried out by simple mixing at the desired elevated temperature.Alternatively, the metalpyridine interaction product and Water may bemixed at a lower temperature and subsequently or simultaneously heatedto the desired elevated temperature. This heating may be carried out ina subsequent operation, for ex ample a distillation operation, and notnecessarily during the treatment stage, although the vigorous reactionwhich takes place during the water treatment is a convenient source ofheat. Conveniently, the process is carried out by adding cold waterslowly with stirring to the metal-pyridine interaction product at such arate that the mixture is maintained at the desired temperature with-outoverheating; cooling may be applied if desired in order to assist this.

If desired, the metal pyridine interaction product (or the mixturecontaining this with excess pyridine) may be diluted with an inertliquid before treatment with water. Suitable inert liquids for thispurpose include hydrocarbons, for example trimethylbenzenes.

The proportion of water to be used should be at least 1 mole, and ispreferably between 1.75 and 2.5 moles, for each equivalent of metal inthe metal-pyridine interaction product. Larger proportions may be usedif desired, but excessive dilution may make subsequent isolation of theproduct more difficult. Smaller proportions tend to give less completereaction and to make the reaction mixture thicker and less easy tohandle.

In the case of treatment of a sodium-pyridine interaction product, wefind it especially advantageous to use a proportion of water which issubstantially 2.2 moles for each equivalent of sodium used. With thisproportion of water, the sodium hydroxide formed during the treatmentseparates out as a liquid aqueous phase which contains substantially allthe water and leaves the liquid organic phase (containing the bipyridylsand excess pyridine) substantially dry. If the proportion of water isreduced there is a tendency for the sodium hydroxide to separate insolid form, and if the proportion of water is increased the organicphase will retain more water. This form of our process is especiallyadvantageous as it provides a very simple and efiicient method forseparating the sodium hydroxide which avoids chemical treatment andwasteful filtration techniques, and also avoids the need for a separatedrying operation before further treatment of the crudebipyridyl/pyridine mixture, for example by distillation. In this case,the mixture produced by treatment of the metal-pyridine interactionproduct with water may conveniently be maintained at a temperature above80 C. but below its boiling point, and preferably at about 100 C., andthen allowed to settle into two liquid phases and the aqueous sodiumhydroxide layer separated and removed. The mixture is preferably kepthot, as indicated, to reduce the possibility of solidification of theaqueous sodium hydroxide phase, and the organic phase thus obtained maycontain as little as 0.1% to 0.2% of water by weight.

The exclusion of air or oxygen may be effected to a satisfactory degreeby carrying out the process in a vessel which has been purged withnitrogen and, preferably, by passing a slow stream of nitrogen throughthe vessel during the addition of the water. It is not necessary to takeprecautions to exclude the air or oxygen absolutely, and the presence ofsmall traces in the nitrogen, or dissolved in the water is notdetrimental.

The course of the reaction is obscure, but reaction is rapid and isusually completed within about an hour.

The isolation of the bipyridyls may be carried out in known manner, forexample by fractional distillation and/ or crystallisation of theproduct. An especially convenient method is that more fully described incopending application, Serial No. 260,883, filed February 25, 1963, nowUS. Patent 3,195,642, wherein the crude product containing bipyridyls isfirst dissolved in aqueous acid and any insoluble matter discarded, andthe resulting aqueous acid solution is neutralised and extracted with awater-immiscible organic solvent, preferably at an elevated temperature.The bipyridyls are thus obtained as a solution in the water-immiscibleorganic solvent, and can be recovered by evaporation of the solvent. The4:4,- bipyridyl can be recovered in the form of its hydrate, as is morefully described in copending application, Serial No. 260,882, filedFebruary 25, 1963, now US. Patent 3,159,641, for example by adding waterto a cold solution of the mixed bipyridyls in a water-immiscible organicsolvent, as may for example be obtained by the extraction processmentioned above.

The process of the present invention has the advantage of simplifyingthe conversion of pyridine to bipyridyls by providing generally greaterease of working than the prior art methods. Moreover, we avoid many ofthe disadvantages and hazards associated with the earlier processes,

and in particular we avoid the necessity for a long oxidation stage, therisk of forming explosive pyridine/ oxygen mixtures, the loss ofpyridine and products by volatilisation in a stream of gaseous oxidisingagent, and we minimise the requirements for streams of inert gas throughthe apparatus and the formation of by-products.

The crude mixture of bipyridyls produced by the process of the presentinvention in some cases contains a higher proportion of the 4:4'-isomerthan the crude bipyridyls made by conventional oxidation techniques.

The invention is illustrated but not limited by the following examplesin which the parts and percentages are by weight.

Example 1 Sodium metal (46 parts, 2 equivalents) in the form of adispersion in trimethylbenzene (92 parts) was added during 45 minutes topyridine (632 parts, 8 moles), stirred in an atmosphere of nitrogen,with cooling so that the temperature was maintained at 90 C. Afteraddition of sodium was complete the temperature of the mixture wasmaintained at 90 C. for 15 minutes with continued stirring, and thenwater parts, 2.2 moles per equivalent of sodium) was added continuously,the initial vigorous heat of reaction being removed by cooling so thatthe temperature of the mixture remaingd between and C. The addition ofwater was made over a period of 15 minutes, after which time stirringwas maintained for a further 15 minutes. The colour of the reactionproduct turned from black to brown during the addition of water. Theproduct was then heated to C. and held at this temperature withoutstirring for one hour, after which time the upper organic layer (740parts) was separated from the lower aqueous layer (125 parts). Less than1 part of the 80 parts of caustic soda formed in the reaction remainedin the upper layer after the separation and less than 1 part of pyridinewas drawn ed with the lower aqueous layer.

The organic layer was then fractionally distilled and from it wasrecovered pyridine (476 parts) and a mixture consisting of2:2'-bipyridyl (0.2 part), 2:4-bipyridyl (5 parts) and 4:4-bipyridyl (49parts).

Example 2 The procedure of Example 1 was repeated except that theinteraction of the sodium and pyridine, and the subsequent addition ofwater, were carried out at 100 C. The products recovered were pyridine(471 parts) and a mixture consisting of 2:2'-bipyridyl (0.2 part), 2:4bipyridyl (4 parts) and 4:4-bipyridyl (42 parts).

Example 3 A mixture of 12 parts of magnesium turnings and 395 parts ofpyridine was heated under reflux conditions, interaction was initiatedby addition of 2 parts of a 33% dispersion of sodium metal in trimethylbenzene, and then interaction was continued for 2 hours while a streamof nitrogen was passed through the reaction vessel. 35 parts of water (2moles per equivalent of magnesium) were then added with stirring during15 minutes, and the resulting mixture was stirred for a further 15minutes and then fractionally distilled. There were thus recoveredpyridine (288 parts) and a mixture consisting of 2:2-bipyridyl (1 part),2:4-bipyridyl (3 parts), and 4:4- bipyridyl (41 parts). This yield of4:4'-bipyridyl corresponded to 38% of theory, based on the pyridineconsumed.

Example 4 A mixture of 36.4 parts of magnesium turnings and 1264 partsof pyridine was heated under reflux conditions, interaction wasinitiated by addition of 3 parts of a 33% dispersion of sodium metal intrimethyl benzene, and then interaction was continued for 6 hours at C.to C. while a stream of nitrogen was passed through the reaction vessel.parts of water (2.2 moles per equivalent of magnesium metal) were thenadded with stirring during 30 minutes while the temperature of themixture was maintained at 105 to 110 C. A portion of the reactionproduct (one half, i.e. 710 parts) was fractionally distilled, and theproducts thereby obtained were pyridine (419 parts) and a mixtureconsisting of 2:2-bipyridyl (4 parts), 2:4'-bipy.ridyl (12 parts) and4:4-bipyridyl (63 parts). The yield of 4:4-bipyridyl corresponded to 30%of theory, based on the pyridine consumed.

Example5 A mixture of 132 gms. of dry pyridine (water content estimatedas 0.01% by Karl Fischer method) and 4 gms. of magnesium turnings wasstirred and heated to reflux in an atmosphere of nitrogen and treatedwith 2 m1. of a 25% dispersion of sodium in trimethyl benzene. Therefluxing was continued for 1 hour 25 minutes, and then the reactionmixture was cooled to 90 C. and 25 ml. of water were added duringminutes. Analysis of the product showed the present of 14.3 gms. of4:4'-bipyridyl. There were also recovered 100 gms. of un changedpyridine.

Example 6 The procedure of Example 5 was repeated except that 200 ml. ofdry oxygen-free trimethyl benzene (a commercial mixture of isomers) wereadded to the hot re action mixture, which was then cooled with stirringto ambient temperature (about C.) and treated with ml. of water. Theamount of 4:4-bipyridyl formed was found to be 14.6 gms., and 100 gms.of unchanged pyridine were recovered.

Example 7 The procedure of Example 5 was repeated up to the completionof the refluxing, and then the reaction mixture was distilled at reducedpressure up to a temperature of 80 C. to remove unchanged pyridine while200 m1. of dry oxygen-free trimethylbenzene were added. The resultingmixture was cooled to ambient temperature with stirring and 25 ml. ofwater were added at that temperature. The amount of 4:4-bipyridyl thusformed was found to be 14.6 gms., and 98 gms. of unchanged pyridine wererecovered.

Example 8 Interaction of a mixture of 10 gms. of aluminium powder and399 gms. of dry pyridine was initiated by 3 gms. of mercuric chlorideand continued for 3.75 hours at 116 C. To the resulting mixture werethen added 25 gms. of water. The amount of 4:4'-bipyridyl formed was14.3 gms. (corresponding to an efliciency of 16% of theory on thealuminium or 17.4% on the pyridine consumed).

Example 9 Interaction of a mixture of aluminium powder (10 gms.) and drypyridine (150 gms.) was initiated by 3 gm. of mercuric chloride,followed by addition of 150 gms. of N:N-dimethylaniline and continuedrefluxing for 3.75 hours at 116 C. The mixture was then treated with 25gm. of water. The amount of 4:4'-bipyridyl thus formed was found to be1.7 gm. (2% efliciency on the aluminium used and 7% on the pyridineconsumed).

Example 10 Interaction of mixture of aluminium powder (10 gm.), drypyridine (150 gm.) and N:N-dimethylaniline (250 gm.) was initiated bymercuric chloride (3 gm.) and the mixture was refluxed for 3.75 hours at116 C. The resulting mixture was treated with water (25 gm.). The amountof 4:4'-bipyridyl thus formed was found to be 2.9 gm. (corresponding to3% efficiency on the aluminium or 5% on the pyridine consumed).

6 Example 11 Interaction of a mixture of aluminium powder (10 gm.) anddry pyridine (528 gm.) was initiated by mercuric chloride (3 gm.)followed by sodium (2 gm.). The mixture was the refluxed for 2.5 hoursand then treated with water (15 gm.). The amount of 4:4'-bipyridyl thusformed was found to be 14.3 gms., corresponding to 16% of theory basedon the aluminium or 18% of theory based on the pyridine consumed.

What we claim is:

1. A process for preparing a bipyridyl which comprises interacting apyridine-reactive metal with a compound selected from the groupconsisting of pyridine and alkyl derivatives thereof in the presence ofan excess amount of said compound to provide a metal-pyridineinteraction product, thereafter heating said metal-pyridine interactionproduct to an elevated temperature and treating the same with water toconvert said metal-pyridine interaction product to the desired bipyridylproduct.

2. The process of claim 1 wherein the reactive metal is interacted withsaid compound at a temperature of at least 70 C.

3. The process of claim 1 wherein the excess amount of said compound ispresent when said metal-pyridine interaction product is treated withwater.

4. The process of claim 1 wherein the treatment with Water is carriedout at a temperature of at least 40 C.

'5. The process of claim 1 wherein the treatment of said metal-pyridineinteraction product with water is carried out at a temperature betweenC. and C.

6. The process of claim 1 wherein at least one mol of water is used foreach equivalent of metal in the metalpyridine interaction product.

7. The process of claim 1 wherein between 1.75 and 2.5 moles of waterare used for each equivalent of metal in said metal-pyridine interactionproduct.

8. A process for preparing 4:4-bipyridyl which comprises the steps ofinteracting magnesium with a compound selected from the group consistingof pyridine and alkyl derivatives thereof at a temperature of at least70 C. in the presence of an excess amount of said compound to provide amagnesium-pyridine interaction prodnot, and thereafter heating to atemperature of at least 40 C. and treating said magnesium-pyridineinterproduct with at least an equimolar amount of water to convert saidmagnesium-pyridine interaction product to a bipyridyl product consistingprimarily of 4:4'-bipyridyl, and thereafter recovering the4:4'-'bipyridyl from said bipyridyl product.

9. A process for preparing 4:4bipyridyl which comprises the steps ofinteracting aluminium with a compound selected from the group consistingof pyridine and alkyl derivatives thereof at a temperature of at least70 C. in the presence of an excess amount of said compound to provide analuminium-pyridine interaction product, and thereafter heating to atemperature of at least 40 C. and treating said aluminium pyridineinteraction product with at least an equimolar amount of water toconvert said aluminium-pyridine interaction product to a bipyridylproduct consisting primarily of 4:4'-bipyridyl, and thereafterrecovering the 4:4-bipyridyl from said bipyridyl product.

10. A process for preparing 4:4'-bipyridyl which comprises the steps ofinteracting sodium with a compound selected from the group consisting ofpyridine and alkyl derivatives thereof at a temperature of at least 70C. in the presence of an excess amount of said compound to provide asodium-pyridine interaction product, and thereafter heating to atemperature of at least 40 C. and treating said sodium-pyridineinteraction product with at least an equimolar amount of water toconvert said sodium-pyridine interaction product to a bipyridyl productconsisting primarily of 4:4-bipyridyl, and thereafter recovering the4z4' bipyridyl from said bipyridyl product.

11. Process as claimed in claim 10 wherein the proportion of water usedis substantially 2.2 moles for each equivalent of sodium in thesodium-pyridine interaction product.

12. The process of claim 11 wherein a liquid organic phase containingthe bipyridyl product is recovered by separation of the water-treatedproduct at a temperature of at least 80 C. into two liquid phases,followed by removing the aqueous sodium hydroxide phase.

13. The process of claim 12 wherein the separation temperature is about100 C.

14. The process of claim 1 wherein the compound is pyridine.

References Cited by the Examiner UNITED STATES PATENTS OTHER REFERENCESSmith: J.A.C.S., vol. 46, pages 414-419 (1924).

WALTER A. MODANCE, Primary Examiner.

10 JOHN D. RANDOLPH, Examiner.

1. A PROCESS FOR PREPARING A BIPYRIDYL WHICH COMPRISES INTERACTING APYRIDINE-REACTIVE METAL WITH A COMPOUND SELECTED FROM THE GROUPCONSISTING OF PYRIDINE AND ALKYL DERIVATIVES THEREOF IN THE PRESENCE OFAN EXCESS AMOUNT OF SAID COMPOUND TO PROVIDE A METAL-PYRIDINEINTERACTION PRODUCT, THEREAFTER HEATING SAID METAL-PYRIDINE INTERACTIONPRODUCT TO AN ELEVATED TEMPERATURE AND TREATING THE SAME WITH WATER TOCONVERT SAID METAL-PYRIDINE INTERACTION PRODUCT TO THE DESIRED BIPYRIDYLPRODUCT.